New Insights Could Lead to a Better Pneumococcal Vaccine
The discovery of a previously unknown mechanism of immunity may lead to a better way to protect vulnerable children and adults against Streptococcus pneumoniae (pneumococcus) infection. The findings may aid the development of novel pneumococcal vaccines that would be less expensive and cover a greater number of known pneumococcal strains than that currently available. Pneumococcus causes serious infections in children and the elderly, including pneumonia and meningitis (inflammation of the brain). Since 2000, U.S. infants have been routinely immunized against pneumococcus, but most developing countries (where nearly one million children die from pneumococcal infections annually) cannot afford the existing vaccine. Researchers have been studying how natural immunity against pneumococcus develops, and have shown that in addition to antibodies, T-cells can provide broad protection against this pathogen. This new study identifies the specific protective T-cells – so-called TH17 cells – and show that they protect against infection by releasing IL-17, a protein that enables human blood cells to kill pneumococcus in the nose more efficiently. This is significant, since colonizing a person’s nose is the first necessary step of infection. Researchers knew that as children get older, they carry pneumococcus in the nose for shorter periods of time and have less risk of disease, but it hadn’t been known how this resistance develops. This works shows that adults and older children, but not newborn babies, have TH17 cells that target pneumococci, suggesting that exposure to pneumococcus normally leads to production of these cells. In mice, they show directly that exposure to pneumococcus triggers the development of these T cells and shortens the duration of nasal carriage of the pathogen. The investigators also describe an efficient way of measuring TH17 cells, which could help determine whether a new vaccine is rallying an effective response. A vaccine that induces both protective antibodies and T-cell immunity to pneumococcus may be a very effective way to protect against this potentially devastating disease.
Interleukin-17A Mediates Acquired Immunity to Pneumococcal Colonization. 2008 PLoS Pathog 4(9): e1000159
Although anticapsular antibodies confer serotype-specific immunity to pneumococci, children increase their ability to clear colonization before these antibodies appear, suggesting involvement of other mechanisms. We previously reported that intranasal immunization of mice with pneumococci confers CD4+ T cell–dependent, antibody- and serotype-independent protection against colonization. Here we show that this immunity, rather than preventing initiation of carriage, accelerates clearance over several days, accompanied by neutrophilic infiltration of the nasopharyngeal mucosa. Adoptive transfer of immune CD4+ T cells was sufficient to confer immunity to naïve RAG1-/- mice. A critical role of interleukin (IL)-17A was demonstrated: mice lacking interferon-gamma or IL-4 were protected, but not mice lacking IL-17A receptor or mice with neutrophil depletion. In vitro expression of IL-17A in response to pneumococci was assayed: lymphoid tissue from vaccinated mice expressed significantly more IL-17A than controls, and IL-17A expression from peripheral blood samples from immunized mice predicted protection in vivo. IL-17A was elicited by pneumococcal stimulation of tonsillar cells of children or adult blood but not cord blood. IL-17A increased pneumococcal killing by human neutrophils both in the absence and in the presence of antibodies and complement. We conclude that IL-17A mediates pneumococcal immunity in mice and probably in humans; its elicitation in vitro could help in the development of candidate pneumococcal vaccines.
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Tags: Bacteria, Biology, Health, Immunology, Medicine, Microbiology, Science, Vaccines
